The present invention relates to a novel oxabicycloheptane derivative of the following formula and a pharmaceutically acceptable salt thereof: ##STR6## where D is a hydrogen atom, a halogen atom, a hydroxyl group, and alkoxy group, an arylalkoxy group, an acyloxy group, a dialkylcarbamoyloxy group or an amidoalkyloxy group; B is a substituted or unsubstituted phenyl, thienyl or furyl group; A is the group ##STR7## (where l is 0 or 1; m and n are each 1 or more, provided that m+n is an integer of 2-8; R.sup.1 is an alkylamino group, a dialkylamino group, an arylalkylamino group, a morpholino group, a thiomorpholino group, a 1-pyrrolidinyl group, a piperidino group, an N-alkylpiperazinyl group, an N-hydroxyalkylpiperazinyl or a pyrrolizidinyl group; and R.sup.2 is a lower alkyl group or a hydroxy group), or the group ##STR8## (where l, m, n, R.sup.1 and R.sup.2 are each the same as defined above), or the group ##STR9## (where R.sup.3 and R.sup.4 which may be the same or different each represents a hydrogen atom, a lower alkyl group, an alkoxycarbonyl group or an acyl group), or the group ##STR10## (where m, l, n, R.sup.1 and R.sup.2 are each the same as defined above).
The oxabicycloheptane derivative having the formula defined above and pharmaceutically acceptable salts thereof are effective in ameliorating or eliminating the symptoms that appear either as a result of organic disorders in the brain or on account of pathergasia. These compounds also have antidepressant effects and are useful as psychopharmaceuticals.
The term "organic disorders in the brain" as used hereinabove means symptoms resulting from cerebral ischemic disorders such as the sequelae of cerebral infarct, encephalorrhagia and cerebroarteriosclerosis, as well as various organic disorders resulting from senile dementia, dementia presenilis, amnesia, and the sequelae of traumas or operations on the brain. The term "pathergasia" means diseases on psychic functions resulting from mania, depression, neurosis, Parkinson's disease, schizophrenia and schizophrenic disorders, chorea, as well as those resulting from use of drugs and alcohol.
Brain cells maintain an intracellular environment that entirely differs from their ambient environment (extracellular fluids) and continue to live by retaining the difference between these two environments. To this end, energy must be constantly produced and supplied to the brain cells. Most of the energy that is required by nerve cells in the brain is supplied by oxygen and glucose but the brain has a very limited reserve of these energy sources and must be constantly fed with additional supplies from the blood stream.
If a certain disorder occurs in the brain and the supply of oxygen and glucose is discontinued, cacochymia of energy generally occurs progressively and the brain cells will lose their functions with the elapse of time and will eventually collapse organically to become no longer capable of fulfilling their functions. Therefore, in order to ensure a stable supply of the necessary energy sources to the brain tissues and provide a controlled external environment for cranial nerve cells, the human cerebral vessels are equipped with a well developed mechanism for adjusting the blood stream in the brain.
Conventional non-surgical therapy for cerebrovascular disorders has involved the use of a variety of drugs for improving the cerebral circulation, dilating the blood vessels or for improving the brain metabolism. These drugs are effective in ameliorating the subjective symptoms of patients but are little effective in lessening their neurotic or psychic symptoms. In addition, no compound has previously been known that can be used as a psycho-pharmaceutical exhibiting capabilities of brain protection end improving the cerebral circulation as does the compound of the present invention.
The present inventors conducted extensive studies for many years in order to find compounds that would be effective in ameliorating and eliminating symptoms that result either from the aforementioned organic disorders in the brain or on account of pathergasia. As a result, the inventors have found that the novel oxabicycloheptane derivatives of the present invention and pharmaceutically acceptable salts thereof are very effective against the formation of peroxylipids and the deficiency of oxygen in a variety of cranial nerve cells (brain anoxia), two factors that are believed to be closely associated with organic disorders in the brain and pathergasia as described above. In addition, these derivatives and pharmaceutically acceptable salts thereof were found to have surprisingly high activities against depression and to be very useful as psychopharmaceuticals. The present invention has been accomplished on the basis of these findings.